Dysregulation of intracellular Ca2+ homeostasis is associated with various pathological conditions and arrhythmogenesis of the heart.The objective of this study was to investigate the effects of an acute increase in intracellular Ca2+ concentration ([Ca2+] i) on the electrophysiology of ventricular myocytes by mimicking intracellular Ca 2+ overload.The [Ca2+] i was clamped to either a controlled (65-100 nmol L-1) or increased (1 μmol L-1) level.The transmembrane action potentials and ionic currents were recorded using whole-cell patch clamp techniques.We found that the acute increase in [Ca2+] i shortened the action potential duration,reduced the action potential amplitude,maximum depolarization velocity and resting membrane potential,caused delayed after-depolarizations (DADs),and triggered activity--compared with these parameters in the control.The increased [Ca2+] i augmented late I Na in a time-dependent manner,reduced ICaL and IK1,and increased IKr but not IKs.The results of this study can be used to explain calcium overload-induced ventricular arrhythmias.
FAN XinRongMA JiHuaWAN WeiZHANG PeiHuaWANG ChaoWU Lin
